紫杉醇
体内
癌症研究
免疫系统
药物输送
免疫疗法
CD8型
体外
化学
化疗
生物
免疫学
生物化学
遗传学
生物技术
有机化学
作者
Yanghui Bi,Jieya Chen,Yan Li,Bin Song,Qing Li,Tong Zhou,Fajia Yuan,Jintao Wang,Ruiping Zhang
标识
DOI:10.1021/acs.molpharmaceut.4c00514
摘要
As a first-line chemotherapeutic agent, albumin-bound paclitaxel (PA) has a considerable effect on the treatment of various cancers. However, in chemotherapy for hepatocarcinoma, the sensitivity to PA is low owing to the innate resistance of hepatocarcinoma cells; the toxicity and side effects are severe, and the clinical treatment impact is poor. In this study, we present a unique nanodrug delivery system. The ultraviolet (UV)-induced tumor-cell-derived extracellular vesicles (EVs) were isolated and purified by differential centrifugation. Then, PA was loaded by coextrusion to create a vesicle drug delivery system (EVPA). By employing the EV-dependent enhanced retention effect and specific homing effect, EVPA would passively and actively target tumor tissues, activate the immune response to release PA, and achieve the combination therapeutic effect of chemo-immunotherapy on hepatocarcinoma. We demonstrated that the tumor-killing effect of EVPA is superior to that of PA, both in vivo and in vitro and that EVPA can be effectively taken up by hepatocarcinoma and dendritic cells, activate the body's specific immune response, promote the infiltration of CD4+ and CD8+ T cells in tumor tissues, and exert a precise killing effect on hepatocarcinoma cells via chemo-immunotherapy.
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